A system and method of neuromodulation adjunct (add-on) therapy for coma and traumatic brain injury, comprises an implantable lead-receiver and an external stimulator. Neuromodulation is performed using a pulsed electrical stimulation. The external stimulator contains a power source, controlling circuitry,...http://www.google.com/patents/US6564102?utm_source=gb-gplus-sharePatent US6564102 - Apparatus and method for adjunct (add-on) treatment of coma and traumatic brain injury with neuromodulation using an external stimulator

Apparatus and method for adjunct (add-on) treatment of coma and traumatic brain injury with neuromodulation using an external stimulatorUS 6564102 B1

Abstract

A system and method of neuromodulation adjunct (add-on) therapy for coma and traumatic brain injury, comprises an implantable lead-receiver and an external stimulator. Neuromodulation is performed using a pulsed electrical stimulation. The external stimulator contains a power source, controlling circuitry, a primary coil, and predetermined programs. The primary coil of the external stimulator inductively transfers electrical signals to the lead-receiver, which is also in electrical contact with a vagus nerve. The external stimulator emits electrical pulses to stimulate the vagus nerve according to a predetermined program. The predetermined programs have different levels of control, which is password protected. The external stimulator may also be equipped with a telecommunications module to control the predetermined programs remotely.

a) an implantable lead-receiver comprising circuitry, a secondary coil and at least one electrode adapted for stimulating a cranial nerve;

b) an external stimulator comprising a power source, circuitry to emit electrical signals, microprocessor and microcontroller encoded with at least two predetermined programs to control said electrical signals, and a primary coil;

c) said primary coil of said exteroal stimulator and said secondary coil of said implantable lead-receiver being adapted for forming an electrical connection by inductive coupling,

whereby said external stimulator is adapted for controlling the stimulation of said cranial nerve.

2. The apparatus of claim 1 wherein said cranial nerve is the left vagus nerve.

3. The apparatus of claim 1, wherein said external stimulator comprises an override mechanism to manually activate said external stimulator.

7. The apparatus of claim 1, wherein said external stimulator has wireless communication means to control the predetermined programs from a remote location.

8. The apparatus of claim 1, wherein said lead-receiver comprises a lead body with at least one lumen, a lead body insulation, a conductor, at least one electrode, circuitry and a coil.

9. The apparatus of claim 8, wherein said at least one lumen is selected from the group consisting of single, double, triple and coaxial lumens.

10. The apparatus of claim 8 wherein said lead body insulation is selected from the group consisting of polyurethane, silicone, and silicone with polytetrafluoroethylene.

11. The apparatus of claim 8 wherein said lead-receiver body further comprises a coating selected from the group consisting of lubricious PVP, antimicrobial and anti-inflammatory coatings.

12. The apparatus of claim 8 wherein said electrode comprises a material selected from the group consisting of platinum, platinum/iridium alloy, platinum/iridium alloy coated with titanium nitride and carbon.

14. The apparatus of claim 1, wherein said electrical signals comprise at least one variable component selected from the group consisting of the current amplitude, pulse width, frequency and on-off timing sequence, and said at least two predetermined programs controls said variable component of said electrical signals.

17. The apparatus of claim 1, wherein said apparatus comprises means for locking out at least one of the predetermined programs using password protection.

18. A method of neuromodulating a cranial nerve for treatment of coma and traumatic brain injury, comprising;

a) selecting a predetermined program from at least two predetermined programs to control the output of an external stimulator;

b) activating said external stimulator to emit electrical signals in accordance with said predetermined program; and

c) inductively coupling said external stimulator with an implantable stimulus receiver to stimulate a cranial nerve.

19. The method of claim 18, further comprising implanting beneath the skin of a patient said stimulus receiver in direct electrical contact with said cranial nerve.

20. The method of claim 18 wherein the cranial nerve is the vagus nerve.

21. A method for adjunct (add-on) therapy for coma and traumatic brain injury using neuromodulation of a cranial nerve, comprising;

a) providing an implantable lead-receiver comprising circuitry, a secondary coil and at least one electrode to stimulate a cranial nerve;

b) providing an external stimulator comprising circuitry to emit electrical signals, at least two predetermined programs to control said electrical signals, a primary coil coil and a power supply;

c) activating one of said at least two programs of said external stimulator;

d) inductively transferring said electrical signals from said primary coil of external stimulator to said secondary coil of lead-receiver;

whereby said electrical signals stimulate said cranial nerve according to at least one of said at least two predetermined programs.

22. The method of claim 21, wherein said cranial nerve is the vagus nerve.

23. The method of claim 21, wherein said predetermined programs are capable of being modified to modify said electrical signals.

24. The method of claim 21, wherein a proximity sensing means is used for optimally positioning the primary coil.

25. The method of claim 21, wherein said external stimulator has wireless communication means to control the predetermined programs from a remote location.

26. The method of claim 21, wherein said cranial nerve is stimulated by bipolar stimulation.

27. The method of claim 21, wherein said cranial nerve is stimulated by unipolar stimulation.

28. The method of claim 21, wherein the step of activating one of said at least two predetermined programs is manually performed.

29. The method of claim 21, further comprising manually controlling said electrical signals to stimulate said cranial nerve.

30. The method of claim 21, wherein

a) said electrical signals comprise at least one variable component selected from the group consisting of the current amplitude, pulse width, frequency, and on-off timing sequence; and

b) said at least two predetermined programs controls said variable component of said electrical signals.

31. The method of claim 21, further comprising manually disengaging said at least two predetermined programs.

32. The method of claim 21, wherein said method comprises means for locking out at least one of the predetermined programs using password protection.

Description

This is a Continuation-in-Part application of Serial No. 09/727,570 filed Nov. 30, 2000 now Pat. No. 6,356,788, which is a Continuation-in-Part of Serial No. 09/178,060 filed Oct. 26, 1998, now U.S. Pat. No. 6,205,359. Priority is claimed from these applications, and the prior applications being incorporated herein by reference. Further, this application is related to the following applications filed Apr. 17, 2001, entitled,

b) Apparatus and method for adjunct (add-on) treatment of diabetes by neuromodulation with an external stimulator.

c) Apparatus and method for neuromodulation therapy for obesity and compulsive eating disorders using an implantable lead-receiver and an external stimulator.

1. FIELD OF INVENTION

This invention relates generally to a medical device for the treatment of coma and brain injury, more specifically a medical device for adjunct (add-on) treatment of coma and traumatic brain injury by electrical stimulation neuromodulation of a selected nerve or nerve bundle utilizing an implanted lead-receiver and an external stimulator.

BACKGROUND

Coma is an abnormally deep state of unconsciousness with an absence of voluntary response to stimuli and with varying degrees of reflex activity. It represents the extreme of a graded continuum of impairment of consciousness, at the opposite pole of the spectrum from full alertness and awareness of the environment. It is not a single uniform disorder, but may stem from different causes such as trauma, disease, or their condition, and which may be characterized by different levels of consciousness. There are degrees of coma, but no varieties. Coma differs from both sleep and syncope (temporary suspension of consciousness due to generalized cerebral ischemia). Cerebral oxygen uptake is normal in sleep or actually increases during the rapid eye movement stage, but cerebral oxygen uptake is abnormally reduced in coma. The patient is incapable of sensing or responding adequately to external stimuli or inner needs, shows little or no spontaneous movement apart from respiration, and no evidence whatever of mental activity.

At the deepest state of coma there is no reaction to stimuli of any intensity, and corneal, pupillary, pharyngeal, tendon and plantar reflexes are absent. Respiration is slow and sometimes periodic (Cheyne-Stokes respiration) and cardiovascular regulating processes may show signs of failure. Lighter degrees of coma (‘semicoma’) allow partial response to stimulation, though this is imcomplete, mostly nonpurposive and usually consists of ineffectual movements or rubbing and scratching of the stimulated area. Bladder distension may call forth groaning or ill-coordinated motor stirring but the patient is still incontinent. Tendon refexes may or may not be obtainable, and the plantars may be either flexor or extensor. The Glasgow Coma Scale has proved its usefulness for the grading of depth of coma.

Coma needs to be distinguished from deep sleep and from stupor. In deep sleep and in coma the pictures may be closely similar on superficial observation. But the sleeper can be roused again to normal consciousness by the efforts of the examiner. He may wake spontaneously or unaccustomed stimuli, or in response to inner sensations such as hunger or bladder distension. In sleep there is sporadic continuing mental activity in the form of dreams that leave traces in memory. The distinguishing features usually accepted are that in coma the eyes remain shut even in response to strong arousal stimuli, do not resist passive opening, and do not appear to be watchful or follow moving objects; movements in response to stimulation are never purposeful, and there is no subsequent recall of events or inner fantasies from the time in question.

The Glasgow Coma Scale is now routinely used for acutely head-injured patients. It has proved to be of considerable predictive value in pointing to long-term outcome, in terms of both survival and ultimate levels of disability. The patient's clinical state is charted regularly on a number of graded parameters: motor responsiveness (no response, extensor response to pain, flexor response, localizing response, obeying commands), verbal performance (nil, without recognizable words, no sustained exchange possible, confused conversation, orientated for person, place and time) an eye opening (nil, in response to pain, in response to speech, spontaneously). Numerical scores are summated for the best responses obtained under each category at a defined point in time. In this way useful predictions can be made, often with 24 hours of injury and more certainly within the first week.

As shown in FIG. 1 recovery from a moderate or severe brain trauma typically involves a progression through a sequence of neurobehavioral syndromes. The initial stage of severely head-injured patients is coma. When consciousness is recovered, a period of delirium and then post-traumatic amnesia is typically seen (stage II). The retrograde component of post-traumatic amnesia is the failure to recall events occurring before the head injury. The anterograde component of post-traumatic amnesia is the failure to store and recall ongoing events occurring since the head injury.

In the system and method of this invention, coma and the residual effects of traumatic brain injury are treated by electrical stimulation neuromodulation of the afferent vagal nerve fibers with an external stimulator with predetermined programs. Since a large percentage of patients with traumatic head injury eventually develop epilepsy which also impedes functional recovery, the anti-epileptic effects of vagus nerve stimulation would also be beneficial.

The vagus nerve 54 provides an easily accessible, peripheral route to modulate central nervous system (CNS) function. Other cranial nerves can be used for the same purpose, but the vagus nerve 54 is preferred because of its easy accessibility. In the human body there are two vagus nerves (VN), the right VN and the left VN. Each vagus nerve is encased in the carotid sheath along with the carotid artery and jugular vein. The innervation of the right and left vagus nerves is different. The innervation of the right vagus nerve is such that stimulating it results in profound bradycardia (slowing of the heart rate). The left vagus nerve has some innervation to the heart, but mostly innervates the visceral organs such as the gastrointestinal tract. It is known that stimulation of the left vagus nerve does not cause any significant deleterious side effects.

Neuromodulation

One of the fundamental features of the nervous system is its ability to generate and conduct electrical impulses. These can take the form of action potentials, which is defined as a single electrical impulse passing down an axon, and is shown schematically in FIG. 2. The top portion of the figure shows conduction over mylinated axon (fiber) and the bottom portion shows conduction over nonmylinated axon (fiber). These electrical signals will travel along the nerve fibers.

The nerve impulse (or action potential) is an “all or nothing” phenomenon. That is to say, once the threshold stimulus intensity is reached an action potential 7 will be generated. This is shown schematically in FIG. 3. The bottom portion of the figure shows a train of action potentials.

Most nerves in the human body are composed of thousands of fibers of different sizes. This is shown schematically in FIG. 4. The different sizes of nerve fibers, which carry signals to and from the brain, are designated by groups A, B, and C. The vagus nerve, for example, may have approximately 100,000 fibers of the three different types, each carrying signals. Each axon or fiber of that nerve conducts only in one direction, in normal circumstances.

In a cross section of peripheral nerve it is seen that the diameter of individual fibers vary substantially. The largest nerve fibers are approximately 20 μm in diameter and are heavily myelinated (i.e., have a myelin sheath, constituting a substance largely composed of fat), whereas the smallest nerve fibers are less than 1 μm in diameter and are unmyelinated. As shown in FIG. 5, when the distal part of a nerve is electrically stimulated, a compound action potential is recorded by an electrode located more proximally. A compound action potential contains several peaks or waves of activity that represent the summated response of multiple fibers having similar conduction velocities. The waves in a compound action potential represent different types of nerve fibers that are classified into corresponding functional categories as shown in the table below,

Conduction

Fiber

Fiber

Velocity

Diameter

Type

(m/sec)

(μm)

Myelination

A Fibers

Alpha

70-120

12-20

Yes

Beta

40-70

5-12

Yes

Gamma

10-50

3-6

Yes

Delta

6-30

2-5

Yes

B Fibers

5-15

<3

Yes

C Fibers

0.5-2.0

0.4-1.2

No

The diameters of group A and group B fibers include the thickness of the myelin sheaths. Group A is further subdivided into alpha, beta, gamma, and delta fibers in decreasing order of size. There is some overlapping of the diameters of the A, B, and C groups because physiological properties, especially in the form of the action potential, are taken into consideration when defining the groups. The smallest fibers (group C) are unmyelinated and have the slowest conduction rate, whereas the myelinated fibers of group B and group A exhibit rates of conduction that progressively increase with diameter.

Compared to unmyelinated fibers, myelinated fibers are typically larger, conduct faster, have very low stimulation thresholds, and exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (μs), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1,000 μs) and a higher amplitude for activation. Because of their very slow conduction, C fibers would not be highly responsive to rapid stimulation. Selective stimulation of only A and B fibers is readily accomplished. The requirement of a larger and wider pulse to stimulate the C fibers, however, makes selective stimulation of only C fibers, to the exclusion of the A and B fibers, virtually unachievable inasmuch as the large signal will tend to activate the A and B fibers to some extent as well.

The vagus nerve is composed of somatic and visceral afferents and efferents. Usually, nerve stimulation activates signals in both directions (bi-directionally). It is possible however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally). The vast majority of vagus nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the skull. The central projections terminate largely in the nucleus of the solitary tract, which sends fibers to various regions of the brain (e.g., the thalamus, hypothalamus and amygdala).

Vagus nerve stimulation is a means of directly affecting central function. As shown in FIG. 6, cranial nerves have both afferent pathway 19 (inward conducting nerve fibers which convey impulses toward the brain) and efferent pathway 21 (outward conducting nerve fibers which convey impulses to an effector). The vagus nerve 54 is composed of 80% afferent sensory fibers carrying information to the brain from the head, neck, thorax, and abdomen. The sensory afferent cell bodies of the vagus reside in the nodose ganglion and relay information to the nucleus tractus solitarius (NTS).

FIG. 7 shows the nerve fibers traveling through the spinothalamic tract to the brain. The afferent fibers project primarily to the nucleus of the solitary tract (FIG. 8) which extends throughout the length of the medulla oblangata. A small number of fibers pass directly to the spinal trigeminal nucleus and the reticular formation. As shown schematically in FIG. 8, the nucleus of the solitary tract has widespread projection to cerebral cortex, basal forebrain, thalamus, hypothalamus, amygdala, hippocampus, dorsal raphe, and cerebellum. In summary, neuromodulation of the vagal nerve fibers attempt to cause arousal because of the connections of the nucleus tractus solitarus to the appropriate centers in the brain.

PRIOR ART

One type of medical device prior art therapy for coma and traumatic brain injury, is generally directed to the use of an implantable lead and an implantable pulse generator technology or “cardiac pacemaker like” technology, or stimulation with an implantable Neurocybernetic Prosthesis. In the prior art, the pulse generator is programmed via a “personnel computer (PC)” based programmer that is adapted with a programmer wand which is placed on top of the skin over the pulse generator implant site, as is shown in FIG. 9. Also in the prior art each parameter is programmed independent of the other parameters. Therefore, millions of different combinations of programs are possible. In the current patent application, approximately nine programs are pre-selected.

U.S. Pat. No. 3,796,221 (Hagfors) is directed to controlling the amplitude, duration and frequency of electrical stimulation applied from an externally located transmitter to an implanted receiver by inductively coupling. Electrical circuitry is schematically illustrated for compensating for the variability in the amplitude of the electrical signal available to the receiver because of the shifting of the relative positions of the transmitter-receiver pair. By highlighting the difficulty of delivering consistent pulses, this patent points away from applications such as the current application, where consistent therapy needs to be continuously sustained over a prolonged period of time. The methodology disclosed is focused on circuitry within the receiver, which would not be sufficient when the transmitting coil and receiving coil assume significantly different orientation, which is likely in the current application. The present invention discloses a novel approach for this problem.

U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara) generally disclose animal research and experimentation related to epilepsy and the like and are directed to stimulating the vagas nerve by using “pacemaker-like” technology, such as an implantable pulse generator. The pacemaker technology concept consists of a stimulating lead connected to a pulse generator (containing the circuity and DC power source) implanted subcutaneously or submuscularly, somewhere in the pectoral or axillary region, with an external personal computer (PC) based programmer. Once the pulse generator is programmed for the patient, the fully functional circuity and power source are fully implanted within the patient's body. In such a system, when the battery is depleted, a surgical procedure is required to disconnect and replace the entire pulse generator (circuitry and power source). These patents neither anticipate practical problems of an inductively coupled system for adjunct therapy of epilepsy, nor suggest solutions to the same for an inductively coupled system for adjunct therapy of partial complex or generalized epilepsy.

U.S. Pat. No. 5,571,150 (Wernicke et al) is generally directed to treatment of coma by electrical nerve stimulation. The methods disclosed in this patent are either acute treatment by positioning an esophageal electrode in the patient, or using an entirely implantable system such as neurocybernetic prostheses for neuromodulation treatment of coma.

U.S. Pat. No. 5,304,206 (Baker, Jr. et al) is directed to activation techniques for implanted medical stimulators. The system uses either a magnet to activate the reed switch in the device, or tapping which acts through the piezoelectric sensor mounted on the case of the implanted device, or a combination of magnet and tapping sequence.

U.S. Pat. No. 4,573,481 (Bullara) is directed to an implantable helical electrode assembly configured to fit around a nerve. The individual flexible ribbon electrodes are each partially embedded in a portion of the peripheral surface of a helically formed dielectric support matrix.

U.S. Pat. No. 4,979,511 (Terry) discloses a flexible, helical electrode structure with an improved connector for attaching the lead wires to the nerve bundle to minimize damage.

Apparatus and method for neuromodulation, in the current application has several advantages over the prior art implantable pulse generator. The external stimulator described here can be manufactured at a fraction of the cost of an implantable pulse generator. The therapy can be freely applied with consideration of battery depletion. Surgical replacement of pulse generator is avoided. The programming is much simpler, and can be adjusted by the patient within certain limits for patient comfort. And, the implanted hardware is significantly less.

SUMMARY OF THE INVENTION

The system and method of the current invention also overcomes many of the disadvantages of the prior art by simplifying the implant and taking the programmability into the external stimulator. Further, the programmability of the external stimulator can be controlled remotely, via the wireless medium, as described in a co-pending application. The system and method of this invention uses the patient as his own feedback loop. Once the therapy is prescribed by the physician, the patient can receive the therapy as needed based on symptoms, and the nurse can adjust the stimulation within prescribed limits.

The present invention is directed to system and methods for adjunct (add-on) electrical neuromodulation therapy for coma and traumatic brain injury using an external stimulator with predetermined programs. The system consists of an implantable lead-receiver containing passive circuitry, electrodes adapted for stimulation of the vagus nerve, and a coil for coupling to the external stimulator. The external stimulator contains electronic circuitry to emit electric pulses, power source, primary coil, and predetermined programs. The external primary coil and subcutaneous secondary coil are inductively coupled. The stimulation is according to pre-packaged programs.

In one aspect of the invention the pulse generator contains a limited number -of predetermined programs packaged into the stimulator, which can be accessed directly without a programmer. The limited number of programs can be any number of programs even as many as 100 programs, and such a number is considered within the scope of this invention.

In another feature of the invention, the system provides for proximity sensing means between the primary (external) and secondary (implanted) coils. Utilizing current technology, the physical size of the implantable lead-receiver has become relatively small. However, it is essential that the primary (external) and secondary (implanted) coils be positioned appropriately with respect to each other. The sensor technology incorporated in the present invention aids in the optimal placement of the external coil relative to a previously implanted subcutaneous coil. This is accomplished through a combination of external and implantable or internal components.

In another feature of the invention, the external stimulator has predetermined programs, as well as a manual “ON” and “OFF” button. Each of these programs has a unique combination of pulse amplitude, pulse width, frequency of stimulation, “ON” time and “OFF” time. After the therapy has been initiated by the physician, the patient or caretaker has a certain amount of flexibility for adjusting the therapy (level of stimulation). The patient has the flexibility to decrease (or increase) the level of stimulation (within limits). The manual “ON” button gives the patient flexibility to immediately start the stimulating pattern at any time. Of the pre-determined programs, patients do not have access to at least one of the programs, and the locked out programs can be activated only by the physician.

Various other features, objects and advantages of the invention will be made apparent from the following description taken together with the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purpose of illustrating the invention, there are shown in accompanying drawing forms which are presently preferred, it being understood that the invention is not intended to be limited to the precise arrangement and instrumentalities shown.

FIG. 1 is a diagram showing sequence of alternation in memory after a closed head injury.

FIG. 2 is a schematic diagram of myelinated and nonmyelinated axon.

FIG. 3 is a schematic diagram of a single nerve impulse and a train of nerve impulses.

FIG. 4 is a diagram of the structure of a peripheral nerve.

FIG. 5 is a diagram showing recordings of compound action potentials.

FIG. 6 is a schematic diagram of brain showing afferent and efferent pathways.

FIG. 7 is a schematic diagram showing pathways along the spinothalamic tract.

FIG. 8 is a schematic diagram showing relationship of Nucleus of the Solitary Track and how it relays information to other parts of the brain.

FIG. 9 is a prior art figure showing an implantable neurocybernetic prosthesis, and a personnel computer based programmer along with an external sensor.

FIG. 10 is a schematic diagram of a patient in coma with an implanted read receiver and an external stimulator with pre-packaged programs.

FIG. 11A is a diagram showing the implanted lead-receiver in contact with the vagus nerve at the distal end.

FIG. 11B is a diagram showing two coils along their axis in a configuration such that the mutual inductance would be maximum.

FIG. 12 shows external stimulator coupled to the implanted unit.

FIG. 13 is a top-level block diagram of the external stimulator and proximity sensing mechanism.

FIG. 14 is a diagram showing the proximity sensor circuitry.

FIG. 15 is a block diagram of programmable array logic interfaced to the programming station.

FIG. 23B is a schematic diagram of the proximal end of the lead receiver implanted lead receiver.

FIG. 24 is a schematic of the passive circuitry in the implanted lead-receiver.

FIG. 25A is a schematic of an alternative embodiment of the implanted lead-receiver.

FIG. 25B is another alternative embodiment of the implanted lead-receiver.

FIG. 26 is a diagram of a hydrogel electrode.

FIG. 27 is a diagram of a lead-receiver utilizing a fiber electrode at the distal end.

FIG. 28 is a diagram of a fiber electrode wrapped around Dacron polyester.

FIG. 29 is a diagram of a lead-receiver with a spiral electrode.

FIG. 30 is a diagram of an electrode embedded in tissue.

FIG. 31 is a diagram of an electrode containing steroid drug inside.

FIG. 32 is a diagram of an electrode containing steroid drug in a silicone collar at the base of electrode.

FIG. 33 is a diagram of an electrode with steroid drug coated on the surface of the electrode.

FIG. 34 is a diagram of cross sections of implantable lead-receiver body showing different lumens.

DETAILED DESCRIPTION OF THE INVENTION

The following description is of the current embodiment for carrying out the invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of describing the general principles of the invention. The scope of the invention should be determined with reference to the claims.

The system and method of neuromodulation therapy of this invention consists of delivering pulsed electrical stimulation, using an implanted lead-receiver and an external stimulator with predetermined programs of stimulation. The implanted lead-receiver and external stimulator are inductively coupled. The predetermined programs contain unique combination of stimulation parameters for neuromodulation, and differ in the aggressiveness of the therapy. Some of the predetermined programs are “locked-out” to the nursing and support staff, and can be accessed and controlled by the physician only.

Referring now to FIG. 10, which shows a schematic diagram of a patient 32 with an implantable lead-receiver 34 and an external stimulator 42, clipped on to a belt 44 in this case. The external stimulator 42, may alternatively be placed in a pocket or other carrying device. The primary (external) coil 46 of the external stimulator 42 is inductively coupled to the secondary (implanted) coil 48 of the implanted lead-receiver 34. As shown in FIG. 11A, the implantable lead-receiver 34 has circuitry at the proximal end 49, and has two stimulating electrodes at the distal end 61, 62. The negative electrode (cathode) 61 is positioned towards the brain and the positive electrode (anode) 62 is positioned away from the brain. During the surgical implant procedure, the stimulating electrodes are tunneled subcutaneously and the spiral shaped electrodes are wrapped around the vagus nerve 54 which is surgically isolated from the carotid artery 56 and jugular vein 58. The incisions are surgically closed and the chronic stimulation process can begin when the tissues are healed from the surgery.

For therapy to commence, the primary (external) coil 46 is placed on the skin on top of the surgically implanted (secondary) coil 48. An adhesive tape is then placed on the skin 60 and external coil 46 such that the external coil 46, is taped firmly to the skin 60. For efficient energy transfer to occur, it is important that the primary (external) and secondary (internal) coils 46,48 be positioned along the same axis and be optimally positioned relative to each other (FIG. 11B). In the present embodiment, the external coil 46 is connected to proximity sensing circuitry 50. The correct positioning of the external coil 46 with respect to the internal coil 48 is indicated by turning “on” of a light emitting diode (LED) on the external stimulator 42.

Optimal placement of the external (primary) coil 46 is done with the aid of proximity sensing circuitry incorporated in the system. Proximity sensing occurs utilizing a combination of external and implantable or internal components. The internal components contains a relatively small magnet composed of materials that exhibit Giant Magneto-Resistor (GMR) characteristics such as Samarium-cobalt, a coil, and passive circuitry. As shown in FIG. 12, the external coil 46 and proximity sensor circuitry 50 are rigidly connected in a convenient enclosure which is attached externally on the skin. The sensors measure the direction of the field applied from the magnet to sensors within a specific range of field strength magnitude. The dual sensors exhibit accurate sensing under relatively large separation between the sensor and the target magnet. As the external coil 46 placement is “fine tuned”, the condition where the external (primary) coil 46 comes in optimal position, i.e. is located adjacent and parallel to the subcutaneous (secondary) coil 48, along its axis, is recorded and indicated by a light emitting diode (LED) on the external stimulator 42.

FIG. 13 shows an overall block diagram of the components of the external stimulator and the proximity sensing mechanism. The proximity sensing components are the primary (external) coil 46, supercutaneous (external) proximity sensors 198, 202 (FIG. 14) in the proximity sensor circuit unit 50, and a subcutaneous secondary coil 48 with a Giant Magneto Resister (GMR) magnet 53 associated with the proximity sensor unit. The proximity sensor circuit 50 provides a measure of the position of the secondary implanted coil 48. The signal output from proximity sensor circuit 50 is derived from the relative location of the primary and secondary coils 46, 48. The coil sub-assemblies consist of the coil and the associated electronic components, that are rigidly connected to the coil.

The proximity sensors (external) contained in the proximity sensor circuit 50 detect the presence of a GMR magnet 53, composed of Samarium Cobalt, that is rigidly attached to the subcutaneous secondary coil 48. The proximity sensors, are mounted externally as a rigid assembly and sense the actual separation between the coils, also known as the proximity distance. In the event that the distance exceeds the system limit, the signal drops off and an alarm sounds to indicate failure of the production of adequate signal in the secondary implanted circuit 167, as applied in the present embodiment of the device. This signal is provided to the location indicator LED 140.

FIG. 14 shows the circuit used to drive the proximity sensors 198, 202 of the proximity sensor circuit. The two proximity sensors 198, 202 obtain a proximity signal based on their position with respect to the implanted GMR magnet 53. This circuit also provides temperature compensation. The sensors 198, 202 are ‘Giant Magneto Resistor’ (GMR) type sensors packaged as proximity sensor unit 50. There are two components of the complete proximity sensor circuit 51. One component is mounted supercutaneously 50, and the other component, the proximity sensor signal control unit 57 is within the external stimulator 42. The resistance effect depends on the combination of the soft magnetic layer of magnet 53, where the change of direction of magnetization from external source can be large, and the hard magnetic layer, where the direction of magnetization remains unchanged. The resistance of this sensor varies along a straight motion through the curvature of the magnetic field. A bridge differential voltage is suitably amplified and used as the proximity signal.

The Siemens GMR B6 (Siemens Corp., Special Components Inc. New Jersey) is used for this function in the present embodiment. The maximum value of the peak-to-peak signal is observed as the external magnetic field becomes strong enough, at which point the resistance increases, resulting in the increase of the field-angle between the soft magnetic and hard magnetic material. The bridge voltage also increases. In this application, the two sensors 198, 202 are oriented orthogonal to each other.

The distance between the magnet and sensor is not relevant as long as the magnetic field is between 5 and 15 KA/m, and provides a range of distances between the sensors 198, 202 and the magnetic material 53. The GMR sensor registers the direction of the external magnetic field. A typical magnet to induce permanent magnetic field is approximately 15 by 8 by 5 mm3, for this application and these components. However, the sensors 198, 202 are sensitive to temperature, such that the corresponding resistance drops as temperature increases. This effect is quite minimal until about 100° C. A full bridge circuit is used for temperature compensation, as shown in temperature compensation circuit 50 of FIG. 14. The sensors 198, 202 and a pair of resistors 200, 204 are shown as part of the bridge network for temperature compensation. It is also possible to use a full bridge network of two additional sensors in place of the resistors 200, 204.

The signal from either proximity sensor 198, 202 is rectangular if the surface of the magnetic material is normal to the sensor and is radial to the axis of a circular GMR device. This indicates a shearing motion between the sensor and the magnetic device. When the sensor is parallel to the vertical axis of this device, there is a fall off of the relatively constant signal at about 25 mm. separation. The GMR sensor combination varies its resistance according to the direction of the external magnetic field, thereby providing an absolute angle sensor. The position of the GMR magnet can be registered at any angle from 0 to 360 degrees.

The external stimulator shown in FIG. 13, with indicator unit 140 which is provided to indicate proximity distance or coil proximity failure (for situations where the patch containing the external coil 46, has been removed, or is twisted abnormally etc.). Indication is also provided to assist in the placement of the patch. In case of general failure, a red light with audible signal is provided when the signal is not reaching the subcutaneous circuit. The indicator unit 140 also displays low battery status. The information on the low battery, normal and out of power conditions will forewarn the user of the requirements of any corrective actions.

As was shown in FIG. 13, the programmable parameters are stored in a programmable logic 304. The predetermined programs stored in the external stimulator are capable of being modified through the use of a separate Programming Station 77. FIG. 15 shows the Programmable Array Logic Unit 304 and interface unit 312 interfaced to the programming station 77. The programming station 77 can be used to load new programs, change the predetermined programs, or the program parameters for various stimulation programs. The programming station is connected to the Programmable Array Unit 75, shown in FIG. 16 (comprising programmable array logic 304 and interface unit 312) with an RS232-C serial connection. The main purpose of the serial line interface is to provide an RS232-C standard interface. This method enables any portable computer with a serial interface to communicate and program the parameters for storing the various programs. The serial communication interface receives the serial data, buffers this data and converts it to a 16 bit parallel data. The Programmable Array Logic 304 component of Programmable Array Unit 75 receives the parallel data bus and stores or modifies the data into a random access matrix 340 (FIG. 16). This array of data also contains special logic and instructions along with the actual data. These special instructions also provide an algorithm for storing, updating and retrieving the parameters from long-term memory. The Programmable logic Array Unit 304, interfaces with Long Term Memory to store the predetermined programs 71. All the previously modified programs can be stored here for access at any time, as well as, additional programs can be locked out for the patient. The programs consist of specific parameters and each unique program will be stored sequentially in long-term memory. A battery unit 310 is present to provide power to all the components shown above. The logic for the storage and decoding is stored in the Random Addressable Storage Matrix (RASM) 340 (FIG. 16). FIG. 16 shows greater details for the Programmable Logic Array Unit 304. The Input Buffer block 343 is where the serial data is stored in temporary register storage. This accumulation allows for the serial to parallel conversion to occur. The serial to 16 bit parallel block 346 sets up 16 bits of data, as created from the RS232-C serial data. This parallel data bus will communicate the data and the address information. The decoder block 344 decodes address information for the Random Addressable Logic Storage Matrix 340 from which to access the data i.e. programmer parameters. The Output Buffer 342 provides an interface to the Long Term Memory 71.

FIG. 17 shows schematically the details of the interface between the Programmable Array Logic 304 and Interface Unit 312 which is connected to the Predetermined Programs block (Long Term Memory) 71. The patient override 73 is essentially a control scheme for initializing or starting a program at any intermediate point. The Programmable array provides a reconfigurable mechanism to store data and associated instructions for the programs. It supports adding, modifying or retrieving the data from a Random Addressable Logic Storage Matrix 340. This is also a widely accepted scheme for treating “flexible” logic description and control. It is flexible by providing the ability to reprogram and even redesign existing programs previously installed as predetermined programs. It allows the manufacturer or authorized user to create, and modify the programs for execution.

The pulse generator circuitry, shown schematically in FIG. 18, exhibits typical multivibrator functionality. This circuit produces regularly occurring pulses where the amplitude, pulse width and frequency is adjustable. The battery 310 is the main external power source for this circuit. The capacitor 450 is connected in parallel with the battery 310. The combination of transistors 412, 442 and 425, and resistors 410, 444, 446 and 448 acts as a constant current source generated at the collector of transistor 426. The transistor 412 has collector connected to the emitter of transistor 442 and base of transistor 425. The transistors 412 and 442 are connected to provide a constant voltage drop. Likewise, transistor 426 also acts as a diode with a resistor 428 connected in series and further connected to the negative terminal of the line at terminal 460. Capacitor 416 provides timing characteristics and its value helps determine pulse width and pulse frequency. The output of the oscillator appears at terminal 458.

Initially, the capacitor 416 gets charged with current from the path of resistor 434 and 436 while all the transistors are turned off. As the capacitor charges up transistor 432 will become forward biased and current will flow via resistors 430 and 436 from the base to emitter resistors. This action turns on the transistor 418 and the positive voltage from the power supply 310 is made available at the base of transistor 438 through resistor 440. This results in the transistor 438 getting turned on. The conduction of transistor 438 causes capacitor 416 to discharge. The time constant for the charge and discharge of capacitor 416 is determined by value of the resistors 428 and 440 and capacitor 416. After the time constant, transistor 432 turns off, and this in turn turns off transistors 438 and 418. A reset mechanism for this multivibrator can be provided by setting a positive voltage, for example 2.5 volts, to the base of transistor 420. This positive increase in voltage turns on transistor 420 followed by transistor 438. The turning on of transistor 438 discharges the capacitor 416 and the reset operation is complete.

Conventional microprocessor and integrated circuits are used for the logic, control and timing circuits. Conventional bipolar transistors are used in radio-frequency oscillator, pulse amplitude ramp control and power amplifier. A standard voltage regulator is used in low-voltage detector. The hardware and software to deliver the pre-determined programs is well known to those skilled in the art.

The pulses delivered to the nerve tissue for stimulation therapy are shown graphically in FIG. 19. As shown in FIG. 20, for patient comfort when the electrical stimulation is turned on, the electrical stimulation is ramped up and ramped down, instead of abrupt delivery of electrical pulses.

The number of predetermined programs can be any number, say 100, and such a number is considered within the scope of the invention. For patient convenience, less than 20 programs are practical. One embodiment contains nine predetermined programs.

In one arrangement, the predetermined programs are arranged in such a way that the aggressiveness of the therapy increases from program #1 to Program #9. Thus the first three programs provide the least aggressive therapy, and the last three programs provide the most aggressive therapy.

The majority of patients will fall into the category that require an intermediate level of therapy, such as program #5. The above are examples of the predetermined programs that are delivered to the vagus nerve. The actual parameter settings for any given patient may deviate somewhat from the above. As shown schematically in FIG. 13, new predetermined programs can be loaded into the external stimulator 42.

In one embodiment, the external stimulator can also have a telecommunications module, as described in a co-pending application, and summarized here for reader convenience. The telecommunications module has two-way communications capabilities.

FIG. 21 shows conceptually the communication between the external stimulator 42 and a remote hand-held computer. A desktop or laptop computer can be a server 500 which is situated remotely, perhaps at a physician's office or a hospital. The stimulation parameter data can be viewed at this facility or reviewed remotely by medical personnel on a hand-held personal data assistant (PDA) 502, such as a “palm-pilot” from PALM corp. (Santa Clara, Calif.), a “Visor” from Handspring Corp. (Mountain view, Calif.) or on a personal computer (PC) available from numerous vendors. The physician or appropriate medical personnel, is able to interrogate the external stimulator 42 device and know what the device is currently programmed to, as well as, get a graphical display of the pulse train. The wireless communication with the remote server 500 and hand-held PDA 502 would be supported in all geographical locations within and outside the United States (US) that provides cell phone voice and data communication service. The pulse generation parameter data can also be viewed on the handheld devices (PDA) 502.

The telecommunications component of this invention uses Wireless Application Protocol (WAP). The Wireless Application Protocol (WAP) is a set of communication protocols standardizing Internet access for wireless devices. While previously, manufacturers used different technologies to get Internet on hand-held devices, with WAP devices and services interoperate. WAP promotes convergence of wireless data and the Internet. The WAP programming model is heavily based on the existing Internet programming model, and is shown schematically in FIG. 22. Introducing a gateway function provides a mechanism for optimizing and extending this model to match the characteristics of the wireless environment. Over-the-air traffic is minimized by binary encoding/decoding of Web pages and readapting the Internet Protocol stack to accommodate the unique characteristics of a wireless medium such as call drops. Such features are facilitated with WAP.

The key components of the WAP technology, as shown in FIG. 22, includes 1) Wireless Mark-up Language (WML) 400 which incorporates the concept of cards and decks, where a card is a single unit of interaction with the user. A service constitutes a number of cards collected in a deck. A card can be displayed on a small screen. WML supported Web pages reside on traditional Web servers. 2) WML Script which is a scripting language, enables application modules or applets to be dynamically transmitted to the client device and allows the user interaction with these applets. 3) Microbrowser, which is a lightweight application resident on the wireless terminal that controls the user interface and interprets the WML/WMLScript content. 4) A lightweight protocol stack 402 which minimizes bandwidth requirements, guaranteeing that a broad range of wireless networks can run WAP applications. The protocol stack of WAP can comprise a set of protocols for the transport (WTP), session (WSP), and security (WTLS) layers. WSP is binary encoded and able to support header caching, thereby economizing on bandwidth requirements. WSP also compensates for high latency by allowing requests and responses to be handled a synchronously, sending before receiving the response to an earlier request. For lost data segments, perhaps due to fading or lack of coverage, WTP only retransmits lost segments using selective retransmission, thereby compensating for a less stable connection in wireless. The above mentioned features are industry standards adopted for wireless applications and greater details have been publicized, and well known to those skilled in the art.

In this embodiment, two modes of communication are possible. In the first, the server initiates an upload of the actual parameters being applied to the patient, receives these from the stimulator, and stores these in its memory, accessible to the authorized user as a dedicated content driven web page. The physician or authorized user can make alterations to the actual parameters, as available on the server, and then initiate a communication session with the stimulator device to download these parameters.

The physician is also able to set up long-term schedules of stimulation therapy for their patient population, through wireless communication with the server. The server in turn communicates these programs to the neurostimulator. Each schedule is securely maintained on the server, and is editable by the physician and can get uploaded to the patient's stimulator device at a scheduled time. Thus, therapy can be customized for each individual patient. Each device issued to a patient has a unique identification key in order to guarantee secure communication between the wireless server 502 and stimulator device 42.

The second mode of communication is the ability to remotely interrogate and monitor the stimulation therapy on the physician's handheld (PDA) 502.

Moving now to the implantable portion of the system, FIG. 23A shows a diagram of the implanted lead-receiver 34, and FIG. 23B shows a diagram of the proximal end 49 of the lead-receiver 34. The proximal end 49 is a relatively flat portion and contains the electrical components on a printed circuit board. The distal end has the two spiral electrodes 61 and 62 for stimulating the nerve. The passive circuitry and electrodes are connected by electrically insulated wire conductors running within the lead body 59. The lead body 59 is made of reinforced medical grade silicone in the presently preferred embodiment.

The circuitry contained in the proximal end 49 of the implantable lead-receiver 34 is shown schematically in FIG. 24, for the presently preffered embodiment. In this embodiment, the circuit uses all passive components. Approximately 25 turn copper wire of 30 gauge, or comparable thickness, is used for the primary coil 46 and secondary coil 48. This wire is concentrically wound with the windings all in one plane. The frequency of the pulse-waveform delivered to the implanted coil 48 can vary and so a variable capacitor 152 provides ability to tune secondary implanted circuit 167 to the signal from the primary coil 46. The pulse signal from secondary (implanted) coil 48 is rectified by the diode bridge 154 and frequency reduction obtained by capacitor 158 and resistor 164. The last component in line is capacitor 166, used for isolating the output signal from the electrode wire. The return path of signal from cathode 61 will be through anode 62 placed in proximity to the cathode 61 for “Bipolar” stimulation. In the current embodiment bipolar mode of stimulation is used, however, the return path can be connected to the remote ground connection (case) of implantable circuit 167, providing for much larger intermediate tissue for “Unipolar” stimulation. The “Bipolar” stimulation offers localized stimulation of tissue compared to “Unipolar” stimulation and is therefore, used in the current embodiment. Unipolar stimulation is more likely to stimulate skeletal muscle in addition to nerve stimulation. The implanted circuit 167 in this embodiment is passive, so a battery does not have to be implanted. It is however possible to implant a battery source for use of active component logic in the implant.

The circuitry shown in FIGS. 25A and 25B can be used as an alternative, for the implanted lead-receiver. The circuitry of FIG. 25A is a slightly simpler version, and circuitry of FIG. 25B contains a conventional NPN transistor 168 connected in an emitter-follower configuration.

The fabrication of the lead-receiver 34 is designed to be modular. Thus, several different combinations of the components can be packaged without significantly altering the functionality of the device. As shown in FIG. 23A, the lead-receiver 34 components are the proximal end 49 containing coil 48, electrical circuitry 167, and case 78. The lead body 59 containing the conductor 65,66 and the distal end has two electrodes cathode 61 and anode 62. In the modular design concept, several design variables are possible, as shown in the table below.

Table of lead-receiver design variables

Conductor

(connecting

Distal

Proximal

Lead

Lead body-

proximal

End

End

body-

Insulation

Lead-

and distal

Electrode -

Electrode -

Circuitry

Lumens

Materials

Coating

ends)

Material

Type

Bipolar

Polyurethane

Alloy of

Pure

Standard

Nickel-

Platinum

ball

Cobalt

electrode

Unipolar

Double

Silicone

Antimicrobial

Platinum-

Hydrogel

coating

Iridium

electrode

(Pt/IR)

Alloy

Triple

Silicone

Anti-

Pt/Ir coated

Spiral

with

Inflammatory

with Titanium

electrode

Polytetrafluor

coating

Nitride

o-ethylene

(PTFE)

Coaxial

Lubricious

Carbon

Steroid

coating

eluting

Either silicone or polyurethane is a suitable material for the implantable lead-receiver body 59. Both materials have proven to have desirable qualities which are not available in the other. Permanently implantable pacemaker leads made of polyurethane are susceptible to some forms of degradation over time. The identified mechanisms are Environmental Stress Cracking (ESC) and Metal Ion Oxidation (MIO). Silicone on the other hand is a softer material, therefore lead body has to be made bigger. In the presently preferred embodiment silicone re-enforced with polytetrafluroethyene (PTFE) is used.

Nerve-electrode interaction is an integral part of the stimulation system. As a practical benefit of modular design, any type of electrode described below can be used as the distal (cathode) stimulating electrode, without changing fabrication methodology or procedure significantly. When a standard electrode made of platinum or platinum/iridium is placed next to the nerve, and secured in place, it promotes an inflammatory response that leads to a thin fibrotic sheath around the electrode over a period of 1 to 6 weeks. This in turn leads to a stable position of electrode relative to the nerve, and a stable electrode-tissue interface, resulting in reliable stimulation of the nerve chronically without damaging the nerve.

Alternatively other electrode forms that are non-traumatic to the nerve such as hydrogel, platinum fiber, or steroid elution electrodes may be used with this system. The concept of hydrogel electrode for nerve stimulation is shown schematically in FIG. 26. The hydrogel material 100 is wrapped around the nerve 54, with tiny platinum electrodes 102 being pulled back from nerve. Over a period of time in the body, the hydrogel material 100 will undergo degradation and there will be fibrotic tissue buildup. Because of the softness of the hydrogel material 100, these electrodes are non-traumatic to the nerve.

The concept of platinum fiber electrodes is shown schematically in FIG. 27. The distal fiber electrode 104 attached to the lead-receiver 34 may be platinum fiber or cable, or the electrode may be thin platinum fiber wrapped around Dacron polyester or Polyimide 106. As shown in FIG. 28, the platinum fibers 108 may be woven around Dacron polyester fiber 106 or platinum fibers 108 may be braided. At implant, the fiber electrode 104 is loosely wrapped around the surgically isolated nerve, then tied loosely so as not to constrict the nerve or put pressure on the nerve. As a further extension, the fiber electrode may be incorporated into a spiral electrode 105 as is shown schematically in FIG. 29. The two “pigs tail” coil electrodes are made from thin platinum coated braided yarn which is adhered to a substrate in the shape of a “pigs tail” and wraps around the nerve. The braid then continues up a silicone tube lead body.

Alternatively, steroid elution electrodes may be used. After implantation of a lead in the body, during the first few weeks there is buildup of fibrotic tissue in-growth over the electrode and to some extent around the lead body. This fibrosis is the end result of body's inflammatory response process which begins soon after the device is implanted. The fibrotic tissue sheath has the net effect of increasing the distance between the stimulation electrode (cathode) and the excitable tissue, which is the vagal nerve in this case. This is shown schematically in FIG. 30, where electrode 52 when covered with fibrotic tissue becomes the “virtual” electrode 114. Non-excitable tissue is depicted as 120 and excitable tissue as 118. A small amount of corticosteroid, dexamethasone sodium phosphate, which is commonly referred to as “steroid” or “dexamethasone” placed inside or around the electrode, has significant beneficial effect on the current or energy threshold, i.e. the amount of energy required to stimulate the excitable tissue. This is well known to those familiar in the art, as there is a long history of steroid elution leads in cardiac pacing application. It takes only about 1 mg of dexamethasone to produce the desirable effects. Three separate ways of delivering the steroid drug to the electrode nerve-tissue interface are being disclosed here. Dexamethasone can be placed inside an electrode with microholes, it can be placed adjacent to the electrode in a silicone collar, or it can be coated on the electrode itself.

Dexamethasone inside the stimulating electrode is shown schematically in FIG. 31. A silicone core that is impregnated with a small quantity of dexamethasone 121, is incorporated inside the electrode. The electrode tip is depicted as 124 and electrode body as 122. Once the lead is implanted in the body, the steroid 121 elutes out through the small holes in the electrode. The steroid drug then has anti-inflammatory action at the electrode tissue interface, which leads to a much thinner fibrotic tissue capsule.

Another way of having a steroid eluting nerve stimulating electrode, is to have the steroid agent placed outside the distal electrode 91 in a silicone collar 126. This is shown schematically in FIG. 32. Approximately 1 mg of dexamethasone is contained in a silicone collar 126, at the base of the distal electrode 52. With such a method, the steroid drug elutes around the electrode 52 in a similar fashion and with similar pharmacokinetic properties, as with the steroid drug being inside the electrode.

Another method of steroid elution for nerve stimulation electrodes is by coating of steroid on the outside (exposed) surface area of the electrode. This is shown schematically in FIG. 33. Nafion is used as the coating matrix. Steroid membrane coating on the outside of the electrode is depicted as 128. The advantages of this method are that it can easily be applied to any electrode, fast and easy manufacturing, and it is cost effective. With this method, the rate of steroid delivery can be controlled by the level of sulfonation.

A schematic representation of the cross section of different possible lumens is shown in FIG. 34. The lead body 59 can have one, two, or three lumens for conducting cable, with or without a hollow lumen. In the cross sections, 132A-F represents lumens(s) for conducting cable, and 134A-C represents hollow lumen for an aid in implanting the lead.

Additionally, different classes of coating may be applied to the implantable lead-receiver 34 after fabrication. These coatings fall into three categories, lubricious coating, antimicrobial coating, and anti-inflammatory coating.

The advantage of modular fabrication is that with one technology platform, several derivative products or models can be manufactured. As a specific practical example, using a silicone lead body platform, three separate derivative or lead models can be manufactured by using three different electrodes such as standard ball electrode, spiral electrode, or steroid electrode. This is made possible by designing the fabrication steps such that the distal electrodes are assembled at the end, and as long as the electrodes are mated to the insulation and conducting cable, the shape or type of electrode does not matter. Similarly, different models can be produced by taking a finished lead and then coating it with lubricious coating or antimicrobial coating. In fact, considering the design variables disclosed in Table 1, a large number of combinations are possible.

While various embodiments of the present invention have been described in detail, it is apparent that modifications and adaptations of those embodiments will occur to those skilled in the art. However, it is to be expressly understood that such modifications and adaptations are within the spirit and scope of the present invention.